title: Kaposi's sarcoma: etiology and pathogenesis, inducing factors, causal associations, and treatments: facts and controversies.
abstract: Kaposi's sarcoma (KS), an angioproliferative disorder, has a viral etiology and a multifactorial pathogenesis hinged on an immune dysfunction. The disease is multifocal, with a course ranging from indolent, with only skin manifestations to fulminant, with extensive visceral involvement. In the current view, all forms of KS have a common etiology in human herpesvirus (HHV)-8 infection, and the differences among them are due to the involvement of various cofactors. In fact, HHV-8 infection can be considered a necessary but not sufficient condition for the development of KS, because further factors (genetic, immunologic, and environmental) are required. The role of cofactors can be attributed to their ability to interact with HHV-8, to affect the immune system, or to act as vasoactive agents. In this contribution, a survey of the current state of knowledge on many and various factors involved in KS pathogenesis is carried out, in particular by highlighting the facts and controversies about the role of some drugs (quinine analogues and angiotensin-converting enzyme inhibitors) in the onset of the disease. Based on these assessments, it is possible to hypothesize that the role of cofactors in KS pathogenesis can move toward an effect either favoring or inhibiting the onset of the disease, depending on the presence of other agents modulating the pathogenesis itself, such as genetic predisposition, environmental factors, drug intake, or lymph flow disorders. It is possible that the same agents may act as either stimulating or inhibiting cofactors according to the patient's genetic background and variable interactions. Treatment guidelines for each form of KS are outlined, because a unique standard therapy for all of them cannot be considered due to KS heterogeneity. In most cases, therapeutic options, both local and systemic, should be tailored to the patient's peculiar clinical conditions.
authors.affiliation: Department of Dermatology, Second University of Naples, via S. Pansini, 5 - 80131 Naples, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Ruocco
authors.affiliation: Department of Dermatology, Second University of Naples, via S. Pansini, 5 - 80131 Naples, Italy. Electronic address: vincenzo.ruocco@unina2.it.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Ruocco
authors.affiliation: Molecular Biology and Viral Oncology and AIDS Reference Centre, National Cancer Institute, "Fondazione Pascale," via M. Semmola - 80131 Naples, Italy.
authors.forename: Maria Lina
authors.initials: ML
authors.lastname: Tornesello
authors.affiliation: Department of Dermatology, Second University of Naples, via S. Pansini, 5 - 80131 Naples, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Gambardella
authors.affiliation: Dermatology Unit, Kaplan Medical Center, Rehovot 76100 Israel; The School of Medicine, Hebrew University and Hadassah Medical Center, Jerusalem, Israel.
authors.forename: Ronni
authors.initials: R
authors.lastname: Wolf
authors.affiliation: Molecular Biology and Viral Oncology and AIDS Reference Centre, National Cancer Institute, "Fondazione Pascale," via M. Semmola - 80131 Naples, Italy.
authors.forename: Franco M
authors.initials: FM
authors.lastname: Buonaguro
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D000998:Antiviral Agents / Q000627:therapeutic use*; D004358:Drug Therapy / Q000379:methods; D019288:Herpesvirus 8, Human / Q000302:isolation & purification; D006801:Humans; D017410:Practice Guidelines as Topic; D012307:Risk Factors; D012514:Sarcoma, Kaposi / Q000188:drug therapy* / Q000209:etiology*; D012725:Sexual Behavior
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000970:Antineoplastic Agents; D000998:Antiviral Agents